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. 2021 Apr;6(2):100078.
doi: 10.1016/j.esmoop.2021.100078. Epub 2021 Mar 16.

The lung immuno-oncology prognostic score (LIPS-3): a prognostic classification of patients receiving first-line pembrolizumab for PD-L1 ≥ 50% advanced non-small-cell lung cancer

G L Banna  1 , A Cortellini  2 , D L Cortinovis  3 , M Tiseo  4 , J G J V Aerts  5 , F Barbieri  6 , R Giusti  7 , E Bria  8 , F Grossi  9 , P Pizzutilo  10 , R Berardi  11 , A Morabito  12 , C Genova  13 , F Mazzoni  14 , V Di Noia  15 , D Signorelli  16 , A Gelibter  17 , M Macerelli  18 , F Rastelli  19 , R Chiari  20 , D Rocco  21 , S Gori  22 , M De Tursi  23 , P Di Marino  24 , G Mansueto  25 , F Zoratto  26 , M Filetti  7 , M Montrone  10 , F Citarella  27 , R Marco  27 , L Cantini  28 , O Nigro  29 , E D'Argento  30 , S Buti  31 , G Minuti  32 , L Landi  32 , G Guaitoli  6 , G Lo Russo  17 , A De Toma  17 , C Donisi  33 , A Friedlaender  34 , A De Giglio  35 , G Metro  36 , G Porzio  37 , C Ficorella  38 , A Addeo  34
Affiliations

The lung immuno-oncology prognostic score (LIPS-3): a prognostic classification of patients receiving first-line pembrolizumab for PD-L1 ≥ 50% advanced non-small-cell lung cancer

G L Banna et al. ESMO Open. 2021 Apr.

Erratum in

Abstract

Background: To stratify the prognosis of patients with programmed cell death-ligand 1 (PD-L1) ≥ 50% advanced non-small-cell lung cancer (aNSCLC) treated with first-line immunotherapy.

Methods: Baseline clinical prognostic factors, the neutrophil-to-lymphocyte ratio (NLR), PD-L1 tumour cell expression level, lactate dehydrogenase (LDH) and their combination were investigated by a retrospective analysis of 784 patients divided between statistically powered training (n = 201) and validation (n = 583) cohorts. Cut-offs were explored by receiver operating characteristic (ROC) curves and a risk model built with validated independent factors by multivariate analysis.

Results: NLR < 4 was a significant prognostic factor in both cohorts (P < 0.001). It represented 53% of patients in the validation cohort, with 1-year overall survival (OS) of 76.6% versus 44.8% with NLR > 4, in the validation series. The addition of PD-L1 ≥ 80% (21% of patients) or LDH < 252 U/l (25%) to NLR < 4 did not result in better 1-year OS (of 72.6% and 74.1%, respectively, in the validation cohort). Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 [P < 0.001, hazard ratio (HR) 2.04], pretreatment steroids (P < 0.001, HR 1.67) and NLR < 4 (P < 0.001, HR 2.29) resulted in independent prognostic factors. A risk model with these three factors, namely, the lung immuno-oncology prognostic score (LIPS)-3, accurately stratified three OS risk-validated categories of patients: favourable (0 risk factors, 40%, 1-year OS of 78.2% in the whole series), intermediate (1 or 2 risk factors, 54%, 1-year OS 53.8%) and poor (>2 risk factors, 5%, 1-year OS 10.7%) prognosis.

Conclusions: We advocate the use of LIPS-3 as an easy-to-assess and inexpensive adjuvant prognostic tool for patients with PD-L1 ≥ 50% aNSCLC.

Keywords: LDH; PD-L1; immune-checkpoint inhibitor; immunotherapy; neutrophil-to-lymphocyte ratio; non-small-cell lung cancer; performance status; prognostic; steroids.

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Conflict of interest statement

Disclosure AC received speaker fees and grant consultancies from AstraZeneca, MSD, BMS, Roche, Novartis and Astellas. EB received speaker and travel fees from MSD, Astra-Zeneca, Pfizer, Helsinn, Eli-Lilly, BMS, Novartis and Roche; received grant consultancies from Roche and Pfizer. MT received speaker fees and grant consultancies from AstraZeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda and Pierre Fabre. AM received speaker fees from Astra, Roche, BMS, MSD, Boehringer, Pfizer and Takeda. FM received grant consultancies from MSD and Takeda. RG received speaker fees and grant consultancies from AstraZeneca and Roche. AF received grant consultancies from Roche, Pfizer, Astellas and BMS. AA received grant consultancies from Takeda, MSD, BMJ, AstraZeneca, Roche and Pfizer. RC received speaker fees from BMS, MSD, Takeda, Pfizer, Roche and AstraZeneca. CG received speaker fees/grant consultancies from Astra Zeneca, BMS and Boehringer-Ingelheim. GLB personal fees from Janssen Cilag, Boehringer Ingelheim, AstraZeneca and Roche, outside the submitted work. All other authors have declared no conflicts of interest. Data sharing The datasets used during this study are available from the corresponding author upon reasonable request.

Figures

Figure 1
Figure 1
Overall survival by NLR plus PD-L1 or LDH in the training and validation cohorts. LDH, lactate dehydrogenase; NLR, neutrophil-to-lymphocyte ratio; PD-L1, programmed cell death-ligand 1. a Favourable versus poor. b Intermediate versus poor. c Favourable versus intermediate.
Figure 2
Figure 2
Overall survival by combination score of three independent prognostic factors in the training and validation cohorts and all series. Baseline risk factors: performance status ≥2, use of steroids, NLR ≥ 4. CI, confidence interval; HR, hazard ratio; NA, not assessable; NLR, neutrophil-to-lymphocyte ratio; ns, not statistically significant; OS, overall survival. a 0, 1, 2 versus 3; 0, 1 versus 2. b 0 versus 1. c 0, 1, 2, versus 3; 0 versus 1; 0 versus 2. d 1 versus 2. e For all group comparisons.
Figure 3
Figure 3
Overall survival by classification score with LIPS-3 and LIPS-4 in the training, validation and all cohorts. LIPS, Lung Immuno-oncology Prognostic Score; LIPS-3, based on the following three validated and independent prognostic factors: performance status ≥2, use of steroids and NLR ≥ 4; LIPS-4, LIPS-3 plus LDH. CI, confidence interval; HR, hazard ratio; LIPS, Lung Immuno-oncology Prognostic Score; LIPS-3, based on the following three validated and independent prognostic factors: performance status ≥2, use of steroids, NLR ≥ 4; LIPS-4, LIPS-3 plus LDH; NA, not assessable; No., number of patients; ns, not statistically significant; OS, overall survival. a Favourable, Intermediate versus Poor. b Intermediate versus Poor. c Good versus Intermediate. d All group comparisons.
Figure 4
Figure 4
LIPS-3 adjuvant prognostic tool for the first-line treatment of patients with aNSCLC and PD-L1 ≥ 50%. The LIPS-3 consists of the following three validated and independent prognostic factors: ECOG PS ≥ 2, use of pretreatment steroids and NLR ≥ 4. The OS curve refers to all patients according to the LIPS-3 score and corresponds to Figure 3C. For further details see Figure 3 legend. aNSCLC, advanced non-small-cell lung cancer; ECOG PS, Eastern Cooperative Oncology Group performance status; ICIs, immune-checkpoint inhibitors; LIPS, Lung Immuno-oncology Prognostic Score; NLR, neutrophils-to-lymphocytes ratio; OS, overall survival.
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